Selective α_1A-Adrenoceptor Stimulation Induces Mueller’s Smooth Muscle Contraction in an Isolated Canine Upper Eyelid Preparation

Abstract

Purpose: It has been demonstrated that in patients with aponeurotic blepharoptosis, α₁-adrenoceptor stimulation causes the contraction of the upper eyelid tarsal smooth muscle (Mueller’s muscle) and opening of the eye. However, α₁-adrenoceptor subtypes mediating the contraction of Mueller’s muscle are still unclear. This study was designed to identify the α₁-adrenoceptor subtypes in Mueller’s muscle.

Materials and Methods: A newly developed canine upper eyelid preparation was retrogradely perfused with a drug-containing Krebs-Henseleit solution through the angular vein in a temperature-controlled organ chamber. The contraction of the preparation was measured with a force-displacement transducer.

Results: Phenylephrine, an α₁-adrenoceptor agonist, increased the upper eyelid contractile force in a dose-dependent manner (K_0.5 = 110 nmol). Interestingly, the contraction in response to phenylephrine was persistent and hardly recovered to a base line level for more than 100 min after washout of the drug. WB4101 (100 nM), an α_1A- and α_1D-adrenoceptor antagonist, but not BMY7378 (100 nM), a selective α_1D-adrenoceptor antagonist, competitively inhibited the phenylephrine-induced contraction. ABT-866, a selective α_1A-adrenoceptor agonist, increased the upper eyelid contractile force as effectively as phenylephrine in a dose-dependent manner (K_0.5 = 190 nmol), and the contraction continued again for more than 100 min.

Conclusion: These results suggest that selective α_1A-adrenoceptor agonists, such as ABT-866, induce the sustained Mueller’s muscle contraction and may be useful in pharmacological treatment of blepharoptosis.

KEYWORDS::

• α₁-Adrenoceptors
• Blepharoptosis
• Canine
• Eyelid
• Mueller’s smooth muscle

ACKNOWLEDGMENTS

The authors wish to thank Ms. Tomoko Nishizawa and Dr. Shunsuke Yuzuriha for discussion and technical assistance, and Ms. Reiko Sakai for secretarial assistance. They also thank Dr. Robert J. Altenbach for copy-editing the manuscript.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.